High-Throughput Screening of pH-Dependent ß-sheet Self-Assembling Peptide.

pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.

SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.

BACKGROUND: Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear. METHODS: To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays. RESULTS: Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation. CONCLUSIONS: Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.

The Exosome-Mediated Cascade Reactions for the Transfer and Inflammatory Responses of Fine Atmospheric Particulate Matter in Macrophages.

Exposure to atmospheric particulate matter (PM) is a frequent occurrence to humans, and their adverse outcomes have become a global concern. Although PM-induced inflammation is a common phenomenon, a clear picture of the mechanisms underlying exosome-mediated inflammation of PM has not yet emerged. Here, we show that exosomes can mediate the cascade reactions for the transfer of PM and inflammatory responses of macrophages. Specifically, two fine PM2.5, namely F1 (<0.49 µm) and F2 (0.95-1.5 µm), stimulated a substantial release of exosomes from macrophages (THP-1 cells) with the order of F1 > F2, via regulation of the P2X7 receptor (P2X7R). Inhibiting P2X7R with a specific inhibitor largely prevented the secretion of exosomes. In particular, we found that exosomes served as a mediator for the transfer of PM2.5 to the recipient macrophages and activated NF-κB signaling through toll-like receptor 4 (TLR-4), thereby stimulating inflammatory cytokine release and altering the inflammatory phenotype of recipients. Importantly, the exosomes derived from PM2.5-treated macrophages induced the inflammatory responses of lung in mice. Our results highlight that exosomes undergo a secretion-particle transfer-adverse outcome chain in macrophages treated with PM2.5. Given the ubiquitous atmospheric particulate matter, these new findings underscore an urgent need for assessing the secretion of exosomes and their impact on human health via exosome-centric physiological pathways.

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies.

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their noninvasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

Mass spectrometry-based screening identifies circulating immunoglobulinA-α1-microglobulin complex as potential biomarker in immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. Previous studies have proved that renal-deposited IgA in IgAN came from circulating IgA1-containing complexes (CICs). METHODS: To explore the composition of CICs in IgAN, we isolated CICs from IgAN patients and healthy controls and then quantitatively analyzed them by mass spectrometry. Meanwhile, the isolated CICs were used to treat human mesangial cells to monitor mesangial cell injury. Using the protein content and injury effects, the key constituent in CICs was identified. Then the circulating levels of identified key constituent-IgA complex were detected in an independent population by an in-house-developed enzyme-linked immunosorbent assay. RESULTS: By comparing the proteins of CICs between IgAN patients and controls, we found that 14 proteins showed significantly different levels. Among them, α1-microglobulin content in CICs was associated with not only in vitro mesangial cell proliferation and monocyte chemoattractant protein 1 secretion, but also in vivo estimated glomerular filtration rate (eGFR) levels and tubulointerstitial lesions in IgAN patients. Moreover, we found α1-microglobulin was prone to bind aberrant glycosylated IgA1. Additionally, elevated circulating IgA-α1-microglobulin complex levels were detected in an independent IgAN population and IgA-α1-microglobulin complex levels were correlated with hypertension, eGFR levels and Oxford T- scores in these IgAN patients. CONCLUSIONS: Our results suggest that the IgA-α1-microglobulin complex is an important constituent in CICs and that circulating IgA-α1-microglobulin complex detection might serve as a potential noninvasive biomarker detection method for IgAN.

Polymer-KLAK Peptide Conjugates Induce Cancer Cell Death through Synergistic Effects of Mitochondria Damage and Autophagy Blockage.

Nanoscaled polymer-peptide conjugates (PPCs) containing both functional peptides and synthetic polymer comprise a new family of biomaterials that can circumvent the limitation of peptides alone. Our previous work showed that PPCs with the therapeutic peptide KLAK, especially PPCs with shorter PEG spacers and a higher degree of polymerization, exhibit enhanced antitumor effects through disrupting mitochondrial membranes. However, as PPCs have a spherical nanostructure (45-60 nm), this may have other effects besides the conjugated therapeutic peptide KLAK itself when they enter cancer cells. In this research, we compared the proteome differences of U87 cells treated with KLAK, polymer, and their conjugates (P-KLAK) through quantitative proteomics technology. The result reveals that proteins involved in oxidative stress response and the Nrf2/ARE pathway were significantly up-regulated after P-KLAK treatment. Moreover, the overexpression of sequestosome 1, a protein substrate that is selectively incorporated into the formation of autophagosome and degraded by autophagy, is found in our study and has not been reported previously in the study of KLAK toxicity. Additional experiments suggest that upon endocytosis, P-KLAK causes lysosome impairment and results in autophagosomes accumulation. Hence, P-KLAK might induce U87 cell death by autophagy blockage due to lysosome impairment as well as mitochondria damage synergistically.

Bimodal imprint chips for peptide screening: integration of high-throughput sequencing by MS and affinity analyses by surface plasmon resonance imaging.

Peptide probes and drugs have widespread applications in disease diagnostics and therapy. The demand for peptides ligands with high affinity and high specificity toward various targets has surged in the biomedical field in recent years. The traditional peptide screening procedure involves selection, sequencing, and characterization steps, and each step is manual and tedious. Herein, we developed a bimodal imprint microarray system to embrace the whole peptide screening process. Silver-sputtered silicon chip fabricated with microwell array can trap and pattern the candidate peptide beads in a one-well-one-bead manner. Peptides on beads were photocleaved in situ. A portion of the peptide in each well was transferred to a gold-coated chip to print the peptide array for high-throughput affinity analyses by surface plasmon resonance imaging (SPRi), and the peptide left in the silver-sputtered chip was ready for in situ single bead sequencing by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Using the bimodal imprint chip system, affinity peptides toward AHA were efficiently screened out from the 7 × 10(4) peptide library. The method provides a solution for high efficiency peptide screening.

Nanoparticles for inducing Gaucher disease-like damage in cancer cells.

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

Secretome analyses of Aß(1-42) stimulated hippocampal astrocytes reveal that CXCL10 is involved in astrocyte migration.

Amyloid-beta (Aß) aggregation plays an important role in the development of Alzheimer's disease (AD). In the AD brain, amyloid plaques are surrounded by reactive astrocytes, and many essential functions of astrocytes have been reported to be mediated by protein secretion. However, the roles of activated astrocytes in AD progression are under intense debate. To provide an in-depth view of the secretomes of activated astrocytes, we present in this study a quantitative profile of rat hippocampal astrocyte secretomes at multiple time points after both brief and sustained Aß(1-42) stimulation. Using SILAC labeling and LC-MS/MS analyses, we identified 19 up-regulated secreted proteins after Aß(1-42) treatment. These differentially expressed proteins have been suggested to be involved in key aspects of biological processes, such as cell recruitment, Aß clearance, and regulation of neurogenesis. Particularly, we validated the role played by CXCL10 in promoting astrocyte aggregation around amyloid plagues through in vitro cell migration analysis. This research provides global, quantitative profiling of astrocyte secretomes produced on Aß stimulation and hence provides a detailed molecular basis for the relationship between amyloid plaques and astrocyte aggregation; the findings thus have important implications for further investigations into AD development and therapy.

Vascular Pericyte-Derived Exosomes Inhibit Bone Resorption via Traf3.

Purpose: Blood vessels distribute cells, oxygen, and nutrients throughout the body to support tissue growth and balance. Pericytes and endothelial cells form the inner wall of blood vessels, crucial for organ development and tissue homeostasis by producing paracrine signaling molecules. In the skeletal system, pericyte-derived vascular factors along with angiogenic factors released by bone cells regulate angiogenesis and bone formation. Although the involvement of angiogenic factors and skeletal blood vessels in bone homeostasis is relatively clear, the role of pericytes and the underlying mechanisms remain unknown. Here, our objective was to elucidate the significance of pericytes in regulating osteoclast differentiation. Methods: We used tissue staining to detect the coverage of pericytes and osteoclasts in femoral tissues of osteoporotic mice and mice of different ages, analyzing their correlation. We developed mice with conditionally deleted pericytes, observing changes in bone mass and osteoclast activity using micro-computer tomography and tissue staining to detect the regulatory effect of pericytes on osteoclasts. Pericytes-derived exosomes (PC-EVs) were collected and co-cultured with monocytes that induce osteoclast differentiation to detect the effect of the former on the exosomes. Finally, the specific mechanism of PC-EVs regulating osteoclast differentiation was verified using RNA sequencing and Western blotting. Results: Our study indicates a significant correlation between pericytes and age-related bone resorption. Conditional deletion of pericytes activated bone resorption and led to osteopenia in vivo. We discovered that PC-EVs inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, which is mediated by tumor necrosis factor receptor-associated factor 3 (Traf3), negatively regulating osteoclast development and bone resorption. Silencing Traf3 in PC-EVs canceled their inhibitory effect on osteoclast differentiation. Conclusion: Our study provides a novel perspective into the regulatory role of pericytes on bone resorption and may provide potential strategies for developing novel anti-bone resorption therapies.

Localized Instillation Enables In Vivo Screening of Targeting Peptides Using One-Bead One-Compound Technology.

The One-Bead One-Compound (OBOC) library screening is an efficient technique for identifying targeting peptides. However, due to the relatively large bead size, it is challenging for the OBOC method to be applied for in vivo screening. Herein, we report an in vivo Localized Instillation Beads library (LIB) screening method to discover targeting peptides with the OBOC technique. Inspired by localized instillation, we constructed a cavity inside of a transplanted tumor of a mouse. Then, the OBOC heptapeptide library was injected and incubated inside the tumor cavity. After an efficient elution process, the retained beads were gathered, from which three MDA-MB-231 tumor-targeting heptapeptides were discovered. It was verified that the best peptide had 1.9-fold higher tumor accumulation than the commonly used targeting peptide RGD in vivo. Finally, two targeting proteins were discovered as potential targets of our targeting peptide to the MDA-MB-231 tumor. The in vivo LIB screening method expands the scope of OBOC peptide screening applications to discover targeting peptides in vivo feasibly and reliably.

Lycium barbarum polysaccharide modulates gut microbiota to alleviate rheumatoid arthritis in a rat model.

Rheumatoid arthritis (RA) seriously impairs the quality of life of sufferers. It has been shown that Lycium barbarum polysaccharide (LBP), a natural active indigestible ingredient with medicinal and edible functions, can effectively relieve RA, however, whether this effect is related to gut microbiota is not known. This study aimed to explore the RA alleviating mechanism of LBP mediated by gut microbiota using a collagen-induced arthritis rat model. The results showed that LBP significantly changed the gut microflora structure accompanied with the RA alleviation. Specifically, a LBP intervention reduced the relative abundance of Lachnospiraceae_NK4A136_group and uncultured_bacterium_f_Ruminococcaceae and significantly increased the abundance of Romboutsia, Lactobacillus, Dubosiella and Faecalibaculum. The mRNA contents of several colonic epithelial genes including Dpep3, Gstm6, Slc27a2, Col11a2, Sycp2, SNORA22, Tnni1, Gpnmb, Mypn and Acsl6, which are potentially associated to RA, were down-regulated due to the DNA hypermethylation, possibly caused by the elevating content of a bacterial metabolite S-adenosyl methionine (SAM). In conclusion, our current study suggests that LBP alleviated RA by reshaping the composition of intestinal microflora which may generate SAM, inducing DNA hypermethylation of RA-related genes in the host intestinal epithelium and subsequently reducing their expression.

Bacterial Magnetosomes Release Iron Ions and Induce Regulation of Iron Homeostasis in Endothelial Cells.

Magnetosomes (MAGs) extracted from magnetotactic bacteria are well-defined membrane-enveloped single-domain magnetic nanoparticles. Due to their superior magnetic and structural properties, MAGs constitute potential materials that can be manipulated via genetic and chemical engineering for use in biomedical and biotechnological applications. However, the long-term effects exerted by MAGs on cells are of concern in the context of in vivo applications. Meanwhile, it remains relatively unclear which mechanisms are employed by cells to process and degrade MAGs. Hence, a better understanding of MAGs' degradation and fundamental signal modulations occurring throughout this process is essential. In the current study, we investigated the potential actions of MAGs on endothelial cells over a 10-day period. MAGs were retained in cells and found to gradually gather in the lysosome-like vesicles. Meanwhile, iron-ion release was observed. Proteomics further revealed a potential cellular mechanism underlying MAGs degradation, in which a group of proteins associated with vesicle biogenesis, and lysosomal enzymes, which participate in protein hydrolysis and lipid degradation, were rapidly upregulated. Moreover, the released iron triggered the regulation of the iron metabolic profiles. However, given that the levels of cell oxidative damage were relatively stable, the released iron ions were handled by iron metabolic profiles and incorporated into normal metabolic routes. These results provide insights into the cell response to MAGs degradation that may improve their in vivo applications.

Photocatalytic co-production of hydrogen gas and N-benzylidenebenzylamine over high-quality 2D layered In4/3P2Se6 nanosheets.

The concurrent photocatalytic synthesis of hydrogen gas and high-valued chemicals over two-dimensional semiconductors is extremely attractive to alleviate global energy and environmental concerns through directly using sunlight. Herein, a novel layered In4/3P2Se6 nanosheet is synthesized by a space confined chemical vapor conversion method, and it acts as a dual-functional photocatalyst to deliver the co-production of hydrogen gas and N-benzylidenebenzylamine from water reduction and selective benzylamine oxidation. The simultaneous yield of hydrogen gas and N-benzylidenebenzylamine is 895 µmol g-1 and 681 µmol g-1, respectively, within 16-hour continuous reaction involving a small amount of water in acetonitrile solvent. Moreover, 97.4% N-benzylidenebenzylamine selectivity from benzylamine oxidation can be achieved with continuous 10 hour-reaction only in acetonitrile solvent under ambient conditions. Further in situ electron paramagnetic resonance measurements and reaction optimization tests reveal that the reaction mechanism strongly relies on the conditions over the In4/3P2Se6 nanosheet photocatalyst.

Comprehensive role of thermal combined ultrasonic pre-treatment in sewage sludge disposal.

Thermal/ultrasonic pre-treatment of sludge has been proven to break the hydrolysis barriers of sewage sludge (SS) and improve the performance of anaerobic digestion (AD). In this study, the objective was to investigate whether the combination of two pre-treatment methods can achieve better results on the AD of SS. The results indicated that, compared with the control group and separate pre-treatment groups, the thermal combined ultrasonic pre-treatment presented more obvious solubilization of soluble proteins, polysaccharides, and other organic matters in SS. The combined method promoted the dissolution of protein-like substances more effectively, with biogas production increased by 19% and the volatile solid (VS) removal rate improved to above 50% compared with the control group. The capillary suction time is reduced by about 85%, which greatly improved the dewatering performance of SS. In addition, the combined method has advantages in degrading sulfonamide antibiotics, roxithromycin and tetracycline. Particularly, by analyzing the interaction between the degradation of different antibiotics and the composition of dissolved organic matters (DOMs), it was found that the composition of DOMs could affect the degradability of different antibiotics. Among them, the high content of tyrosine-like and tryptophan-like was conducive to the degradation of sulfamethoxazole, and the high content of fulvic acid-like and humic acid-like was conducive to the degradation of roxithromycin and tetracycline. This work evaluated the comprehensive effect of thermal combined ultrasonic pre-treatment on SS disposal and provided useful information for its engineering.

Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study.

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.

CD151 enrichment in exosomes of luminal androgen receptor breast cancer cell line contributes to cell invasion.

Breast cancer is the most common and highly heterogeneous disease in women worldwide. Given the challenges in the treatment of advanced metastatic breast cancer, it is necessary to understand the molecular mechanisms related to disease progression. Exosomes play various roles in the progression of tumors, including promoting the invasion and advancing the distant metastasis. To study the molecular mechanisms related to the progression of luminal androgen receptor (LAR) breast cancer, we first isolated exosomes of MDA-MB-453 cells, a representative cell line of LAR. Through quantitative proteomic analysis, we identified 180 proteins specifically enriched in exosomes after comparing with those in cells, microvesicles, and the 150K supernatant. Among these, CD151, a protein involved in the regulation of cell motility was the most enriched one. CD151-knockdown exosomes reduced the invasion ability of the recipient breast cancer cell and lowered the phosphorylation level of tyrosine-protein kinase Lck, indicating that the invasion of LAR breast cancer may be due to CD151-enriched exosomes. Our work reports for the first time that CD151 was highly abundant in the exosomes of MDA-MB-453 cells and expands the understanding of the development process of LAR subtype, suggesting CD151 may be a potential candidate for the treatment of LAR breast cancer.

E. coli Membrane Vesicles as a Catalase Carrier for Long-Term Tumor Hypoxia Relief to Enhance Radiotherapy.

Hypoxia is one of the most important factors that limit the effect of radiotherapy, and the abundant H2O2 in tumor tissues will also aggravate hypoxia-induced radiotherapy resistance. Delivering catalase to decompose H2O2 into oxygen is an effective strategy to relieve tumor hypoxia and radiotherapy resistance. However, low stability limits catalase's in vivo application, which is one of the most common limitations for almost all proteins' internal utilization. Here, we develop catalase containing E. coli membrane vesicles (EMs) with excellent protease resistance to relieve tumor hypoxia for a long time. Even treated with 100-fold of protease, EMs showed higher catalase activity than free catalase. After being injected into tumors post 12 h, EMs maintained their hypoxia relief ability while free catalase lost its activity. Our results indicate that EMs might be an excellent catalase delivery for tumor hypoxia relief. Combined with their immune stimulation features, EMs could enhance radiotherapy and induce antitumor immune memory effectively.

ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice.

Defective rhodopsin homeostasis is one of the major causes of retinal degeneration, including the disease Retinitis pigmentosa. To identify cellular factors required for the biosynthesis of rhodopsin, we performed a genome-wide genetic screen in Drosophila for mutants with reduced levels of rhodopsin. We isolated loss-of-function alleles in endoplasmic reticulum membrane protein complex 3 (emc3), emc5, and emc6, each of which exhibited defective phototransduction and photoreceptor cell degeneration. EMC3, EMC5, and EMC6 were essential for rhodopsin synthesis independent of the ER associated degradation (ERAD) pathway, which eliminates misfolded proteins. We generated null mutations for all EMC subunits, and further demonstrated that different EMC subunits play roles in different cellular functions. Conditional knockout of the Emc3 gene in mice led to mislocalization of rhodopsin protein and death of cone and rod photoreceptor cells. These data indicate conserved roles for EMC subunits in maintaining rhodopsin homeostasis and photoreceptor function, and suggest that retinal degeneration may also be caused by defects in early biosynthesis of rhodopsin.

A Protein Corona Adsorbed to a Bacterial Magnetosome Affects Its Cellular Uptake.

PURPOSE: It is well known that when exposed to human blood plasma, nanoparticles are predominantly coated by a layer of proteins, forming a corona that will mediate the subsequent cell interactions. Magnetosomes are protein-rich membrane nanoparticles which are synthesized by magnetic bacteria; these have gained a lot of attention owing to their unique magnetic and biochemical characteristics. Nevertheless, whether bacterial magnetosomes have a corona after interacting with the plasma, and how such a corona affects nanoparticle-cell interactions is yet to be elucidated. The aim of this study was to characterize corona formation around a bacterial magnetosome and to assess the functional consequences. METHODS: Magnetosomes were isolated from the magnetotactic bacteria, M. gryphiswaldense (MSR-1). Size, morphology, and zeta potential were measured by transmission electron microscopy and dynamic light scattering. A quantitative characterization of plasma corona proteins was performed using LC-MS/MS. Protein absorption was further examined by circular dichroism and the effect of the corona on cellular uptake was investigated by microscopy and spectroscopy. RESULTS: Various serum proteins were found to be selectively adsorbed on the surface of the bacterial magnetosomes following plasma exposure, forming a corona. Compared to the pristine magnetosomes, the acquired corona promoted efficient cellular uptake by human vascular endothelial cells. Using a protein-interaction prediction method, we identified cell surface receptors that could potentially associate with abundant corona components. Of these, one abundant corona protein, ApoE, may be responsible for internalization of the magnetosome-corona complex through LDL receptor-mediated internalization. CONCLUSION: Our findings provide clues as to the physiological response to magnetosomes and also reveal the corona composition of this membrane-coated nanomaterial after exposure to blood plasma.